Pulmonary delivery of the decapeptide detirelix was studied in briefly anesthetized dogs and the pharmacokinetics were examined following intravenous administration, intratracheal instillation, and aerosol inhalation. Detirelix administrations to the lung gave plasma profiles that were extended over two days, and that differed markedly from those of similarly sized peptides. Absorption from the lung after instillation was slow (Tmax = 6.5 +/- 3.6 h) with a relative bioavailability of 29 +/- 10%. Administration of detirelix-containing aerosols resulted in similar plasma profiles as for administration by instillation. Compartmental and non-compartmental methods of pharmacokinetic analysis indicated no faster absorption from aerosols than from instilled solutions; an absorption rate limiting process may be an explanation. Plasma profiles were not affected by the use of detirelix liquid crystal favoring formulations or destabilizing formulations, and suggested that in situ liquid crystal formation was not an explanation for the slow absorption. No significant changes in pharmacokinetics or systemic uptake were observed during the five-month period of repeated pulmonary administrations. Histopathologic examination revealed the lungs to be essentially normal.